Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.
 ...
PMID:Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. 220 83

Five human rhabdomyosarcoma cell lines were used to investigate the surface expression of HER/erbB receptors, particularly of HER-2, HER-3 and HER-4, by flow cytometry. HER-2 was expressed in 3/5 rhabdomyosarcoma cell lines. HER-3 was expressed in all rhabdomyosarcoma cell lines. None of the rhabdomyosarcoma cell lines investigated showed HER-4 surface expression. To study the biological activity of HER/erbB receptors in rhabdomyosarcomas, cells were cultured in the presence of glial growth factor 2 (GGF-2), a specific ligand of HER-3 that is able to stimulate myogenesis in normal myoblasts. In 3 of 3 human rhabdomyosarcoma cell lines positive for both HER-2 and HER-3 receptors, the treatment with GGF-2 induced a significant increase in myogenic differentiation.
 ...
PMID:Expression of HER/erbB family of receptor tyrosine kinases and induction of differentiation by glial growth factor 2 in human rhabdomyosarcoma cells. 1086 49

Human rhabdomyosarcoma cells express HER/erbB growth factors receptors. Receptors belonging to this family are overexpressed and play a role in many types of epithelial and neural cancer and have been selected as targets for cancer therapy. In this paper EGF-R, HER-2 and HER-3 receptors were tested as therapeutic targets of immunotoxins in human rhabdomyosarcoma. Rhabdomyosarcoma cells were treated with indirect immunotoxins consisting in primary specific murine monoclonal antibodies recognizing EGF-R, HER-2 and HER-3 followed by secondary F(ab')2 antimouse immunoglobulin linked to saporin-S6, a type 1 ribosome-inactivating protein (RIP) from the seeds of Saponaria officinalis. The indirect immunotoxin targeting EGF-R caused a significant inhibition in cell growth and protein synthesis and a strong increase in apoptosis in rhabdomyosarcoma cells, whereas indirect immunotoxins against HER-2 and HER-3 were ineffective. The toxic activity of anti-EGF-R immunotoxin was also observed on rhabdomyosarcoma cells expressing low level of EGF-R. EGF-R could be a novel therapeutic target of immunotoxins in human rhabdomyosarcoma.
 ...
PMID:HER/erbB receptors as therapeutic targets of immunotoxins in human rhabdomyosarcoma cells. 1214 54

Desmoplastic small round cell tumor is a rare tumor typically involving peritoneum. Although the histogenesis of desmoplastic small round cell tumor has yet to be elucidated, immunophenotypical and morphological analysis shows a characteristic divergent phenotype overlapping with other round cell tumors such as Ewing's sarcoma/primitive neuroectodermal tumor, rhabdomyosarcoma, small cell mesothelioma, and carcinoma. Detection of the EWS-WT1 gene fusion is characteristic of desmoplastic small round cell tumor and has been used reliably in tumor diagnosis. In this study, we evaluated the immunophenotype of 23 desmoplastic small round cell tumor cases with the EWS-WT1 gene fusion product identified by reverse transcription-polymerase chain reaction. Paraffin sections were stained with antibodies against calretinin, WT1 (C19), desmin, myoglobin, MyoD, Myf5, myogenin, placental alkaline phosphatase, cytokeratins, MIC2, HER2/neu and c-kit using standard immunohistochemical methods. Immunoreactivity was evaluated semiquantitively by light microscopy. Desmoplastic small round cell tumors showed reactivity with calretinin in 4/21, desmin in 21/23, myoglobin in 5/17, placental alkaline phosphatase in 17/21, HER2/neu in 7/18 (3+ in 1 and 1+ in 6), c-kit in 2/14, MIC2 in 13/23, WT1 in 16/23, CAM5.2 in 21/23, and AE1/3 in 16/23 cases. The most sensitive myogenic and epithelial markers are desmin and CAM 5.2. Although nuclear reactivity of the early myogenic regulatory factors (MyoD, myogenin, Myf5) was not detected, myoglobin immunoreactivity was present in 29% of desmoplastic small round cell tumors. HER2/neu overexpression (3+) and c-kit expression are uncommon in desmoplastic small round cell tumors. A panel of myogenic and epithelial markers should be used to detect the divergent phenotype in desmoplastic small round cell tumors, a key feature in the differential diagnosis. Detection of EWS-WT1 fusion becomes critical for the diagnosis when the characteristic divergent phenotype cannot be detected immunohistochemically.
 ...
PMID:Immunophenotype of desmoplastic small round cell tumors as detected in cases with EWS-WT1 gene fusion product. 1264 Jan 3

Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib, and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with several endocrine agents improve treatment efficacy over endocrine agents alone for hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC). Based on such results, these combinations have been approved for clinical use. Preclinical studies in cell cultures and mouse models proved that CDK4/6i are active against a broad spectrum of solid tumors other than breast cancer, including liposarcoma, rhabdomyosarcoma, non-small cell lung cancer, glioblastoma multiforme, esophageal cancer, and melanoma. The role of CDK4/6i in monotherapy in several solid tumors is currently under evaluation in phase I, II, and III trials. Nowadays, abemaciclib is the only of the three inhibitors that has received approval as single agent therapy for pretreated HR+ HER2- MBC. Here we review biological, preclinical and clinical data on the role of CDK4/6 inhibitors as single agents in advanced solid tumors.
 ...
PMID:CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors. 3063 51

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.
 ...
PMID:Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma. 3266 48